Document Type
Article
Publication Date
2022
Keywords
Uveal Melanoma, BAP1, Intrinsically Disordered Protein (IDP), Intrinsically Disordered Protein Regions (IDPR), Protein–protein Interaction Network
Digital Object Identifier (DOI)
https://doi.org/10.3390/genes13101703
Abstract
Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Genes, v. 13, issue 10, art. 1703
Scholar Commons Citation
Djulbegovic, Mak B.; Taylor, David J.; Uversky, Vladimir N.; Galor, Anat; Shields, Carol L.; and kARP, Carol L., "Intrinsic Disorder in BAP1 and Its Association with Uveal Melanoma" (2022). Molecular Medicine Faculty Publications. 1000.
https://digitalcommons.usf.edu/mme_facpub/1000
